Homeodomain factor Nkx2-3 controls regional expression of leukocyte homing coreceptor MAdCAM-1 in specialized endothelial cells of the viscera

Cheng Chun Wang, Christine Biben, Lorraine Robb, Fatiha Nassir, Louise Barnett, Nicholas O. Davidson, Frank Koentgen, David Tarlinton, Richard P. Harvey

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

Regulated emigration of blood-borne leukocytes plays a defining role in lymphoid organ development, immune surveillance, and inflammatory responses. We report here that mice deficient in the homeobox gene Nkx2-3, expressed in developing visceral mesoderm, show a complex intestinal malabsorption phenotype and striking abnormalities of gut-associated lymphoid tissue and spleen suggestive of deranged leukocyte homing. Mutant Peyer's patches were reduced in number and size, intestinal villi contained few IgA+ plasma cells, and mutant spleens were small and often atrophic, showing fused periarterial lymphoid sheaths, partially merged T and B cell zones, an absent marginal zone, and a dearth of macrophages in red pulp. Semiquantitative RT-PCR analysis and immunohistochemistry revealed down-regulation of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in endothelial cells in which Nkx2-3 is normally expressed. MAdCAM-1 is a member of the immunoglobulin superfamily, acting as an endothelial cell ligand for leukocyte homing receptors L-selectin and α4β7 integrin. Our data suggest a role for a homeodomain factor in establishing the developmental and positional cues in endothelia that regulate leukocyte homing through local control of cellular adhesion and identify MAdCAM-1 as a candidate target gene of Nkx2-3. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)152-167
Number of pages16
JournalDevelopmental Biology
Volume224
Issue number2
DOIs
StatePublished - Aug 15 2000

Keywords

  • Homeobox
  • Lamina propria
  • Leukocyte homing
  • Lymphocyte homing
  • MAdCAM-1
  • NK-2
  • Nkx2-3
  • Peyer's patches
  • Spleen

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